Human serum albumin is capable of binding bilirubin with high affinity, thus sequestering it and mitigat- ing its harmful neurological effects in jaundiced newborns. Despite considerable work indicating that the level of bilirubin in the blood relative to the level of albumin binding sites is a key factor in assessing risk for bilirubin associated brain damage, management of neonatal jaundice remains based upon proxies, such as gestational age and birth weight along with the bilirubin level. A number of methods for assaying the bilirubin level now ex- ist. The common approaches determine the total serum bilirubin by wet chemical methods. Methods to assay reserve albumin binding capacity and unbound (mobilized) bilirubin levels in serum have been developed over the years but none have achieved routine use because they remain cumbersome laboratory tests. The pro- posed work is to develop a point-of-care system (a small fluorometer and disposables) that makes use of bili- rubin's natural fluorescence. Bilirubin bound to albumin produces a fluorescence signal that can be detected in raw blood. Assayed by fluorescence this albumin-bound bilirubin level equates to the total serum bilirubin by standard methods since the unbound bilirubin level is always much smaller until albumin binding approaches saturation. The reserve binding capacity for bilirubin can be measured by adding excess bilirubin to the blood, with the increase in fluorescence being due to the newly bound bilirubin. This approach measures the actual binding capacity and naturally takes into account factors such as albumin levels, competing binding by other solutes and weakened binding sites. The basic studies leading to this fluorometric approach were reported more than thirty years ago and prototype laboratory-bound instruments were devised and tested in clinical settings. At that time new manage- ment guidelines in the absence of binding data coupled with wide use of phototherapy obviated their use. With the current practice of very early release of apparently healthy newborns and susbsequent development of jaundice at home, management has become complicated. Interviews with pediatricians "on the ground" have indicated that an inexpensive and easy to use point-of-care system that requires only a "heel stick" quantity of blood and essentially no manipulation of the specimen, would provide for better management from the ability to provide a stat bilirubin level alone, and binding data would additionally provide guidance in management that may be more efficient and less costly. Use at crib-side should also benefit the management of the jaundiced hospitalized low-birth-weight and sick neonate. While apparently feasible with modern optoelectronic technology, several design and practical chal- lenges exist for the development of such a small point-of-care system. The proposed work will confront and overcome these challenges. PUBLIC HEALTH RELEVANCE: Kernicterus is a preventable brain injury in neonates, and it is reemerging in the USA (1-5). Present-day methods of assaying bilirubin do not take into account a child's ability to safely sequester bilirubin and must be interpreted in terms of gestational age, age, weight and other factors (6). The proposed hematofluorometer directly measures bilirubin binding and reserve bilirubin binding capacity, and has the potentials to be faster, less expensive and available at the point of care.